Direct Aldehyde Homologation Utilized To Construct a Conjugated-Tetraene Hydrocarbon Insect Pheromone

• Published in: Journal of agricultural and food chemistry 2007-03, Vol.55 (6), p.2282-2287
• Main Authors: Petroski, Richard J, Bartelt, Robert J
• Format: Article
• Language: English
• Subjects: (2E,4E,6E,8E)-3,5-dimethyl-7-ethyl-2,4,6,8-undecatetraene; aldehydes; Aldehydes - chemical synthesis; Aldehydes - chemistry; Alkenes - chemical synthesis; Animals; Biological and medical sciences; Carpophilus; Carpophilus lugubris; chemical reactions; Coleoptera - chemistry; Control; Food industries; Fundamental and applied biological sciences. Psychology; hydrocarbons; Indicators and Reagents; insect pests; Integrated pest control; Organophosphonates; pheromones; Pheromones - chemical synthesis; Phytopathology. Animal pests. Plant and forest protection; Protozoa. Invertebrates; synthesis; tetraene hydrocarbons
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf063337e

New phosphonate reagents were developed for the two-carbon homologation of aldehydes to methyl- or ethyl-branched unsaturated aldehydes and used in the practical synthesis of (2E,4E,6E,8E)-3,5-dimethyl-7-ethyl-2,4,6,8-undecatetraene (1), a pheromone of the beetle Carpophilus lugubris. The phosphonate reagents, diethyl ethylformyl-2-phosphonate dimethylhydrazone and diethyl 1-propylformyl-2-phosphonate dimethylhydrazone, contained a protected aldehyde group instead of the usual ester group. A homologation cycle entailed condensation of the reagent with the starting aldehyde, followed by removal of the dimethylhydrazone protective group with a biphasic mixture of dilute HCl and petroleum ether. This robust two-step process replaces the standard three-step aldehyde homologation route using ester-based Horner−Wadsworth−Emmons reagents. The new synthesis of compound 1 from (2E)-2-methyl-2-butenal was run on a 10-g scale and required just five steps (two cycles of condensation and deprotection, followed by a final Wittig olefination) instead of the usual seven. In addition, the Wittig olefination step was simplified and its E-isomer selectivity was improved. The overall yield for the entire synthetic pathway was increased from 20% to 37%, enhancing the commercial potential of Carpophilus pheromones. Keywords: Aldehyde homologation; diethyl ethylformyl-2-phosphonate dimethylhydrazone; diethyl 1-propylformyl-2-phosphonate dimethylhydrazone; sap beetle; Carpophilus lugubris; Nitidulidae